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Computational pathology1,2 has witnessed considerable progress in the development of both task-specific predictive models and task-agnostic self-supervised vision encoders3,4. However, despite the explosive growth of generative artificial intelligence (AI), there have been few studies on building general-purpose multimodal AI assistants and copilots5 tailored to pathology. Here we present PathChat, a vision-language generalist AI assistant for human pathology. We built PathChat by adapting a foundational vision encoder for pathology, combining it with a pretrained large language model and fine-tuning the whole system on over 456,000 diverse visual-language instructions consisting of 999,202 question and answer turns. We compare PathChat with several multimodal vision-language AI assistants and GPT-4V, which powers the commercially available multimodal general-purpose AI assistant ChatGPT-4 (ref. 6). PathChat achieved state-of-the-art performance on multiple-choice diagnostic questions from cases with diverse tissue origins and disease models. Furthermore, using open-ended questions and human expert evaluation, we found that overall PathChat produced more accurate and pathologist-preferable responses to diverse queries related to pathology. As an interactive vision-language AI copilot that can flexibly handle both visual and natural language inputs, PathChat may potentially find impactful applications in pathology education, research and human-in-the-loop clinical decision-making.PathChat, a multimodal generative AI copilot for human pathology, has been trained on a large dataset of visual-language instructions to interactively assist users with diverse pathology tasks. [ABSTRACT FROM AUTHOR]

In the context of wire electrical discharge machining (WEDM), determining the fraction of thermal energy transferred to the workpiece (fc) is crucial for numerical modelling. This information is necessary to anticipate material removal mechanisms and understand thermal behaviour. In this study, two metaphor-less Rao algorithms are modified to solve the inverse heat conduction problem (IHCP) for the estimation of fc during the WEDM process without knowing any prior information on the transient functional form of fc. These two algorithms are compared in terms of accuracy and convergence speed. The Rao-1 algorithm stands out with high accuracy and rapid convergence. To evaluate the algorithm applicability in estimating fc, the following cases are considered: (1) a numerical investigation with artificial Gaussian error in simulated temperature readings and (2) a real-time experiment on WEDM setup with varying discharge currents. The RMS error between the actual and estimated value of fc with SS-304 material during numerical investigation is found to be 562 W/m which is just 0.008 times of heat source. Real-time experiments reveal that the discharge current is directly proportional to the total energy supplied by the wire as well as fc. The fc values estimated by the proposed inverse algorithm with various discharge currents fall within the range of 15–18%, aligning with the existing literature. This shows the proposed methodology is accurate and can be extended to incorporate other machining processes. [ABSTRACT FROM AUTHOR]

This article provides a comprehensive review of the recent literature on various natural fiber and inorganic filler-based polymer composites used in rotational molding (RM). The RM has grown in prominence in various essential applications in recent years. Different industries are working to create lighter components, especially in the automobile and aerospace industries, to improve fuel efficiency and reduce costs. Polymer matrix composites are lightweight, recyclable, corrosion-resistant, and cost-effective. Nonetheless, they are likewise limited in terms of strength, to overcome the polymer's obvious limitations natural fibers and inorganic particle fillers are often added to polymer composites in RM to improve their stiffness and strength and expand their uses. This necessitates a comprehensive study of the various materials available for rotational molding and their influence on the mechanical properties of composites. The variety of materials used in rotational molding is examined and recent advancements are highlighted in the first section. The second section of the discussion focuses on various materials used in rotational molding, their properties, and their advantages and disadvantages. The third section of the paper is dedicated to examining the relationship between the molecular weight of the material and the resulting crystallinity and mechanical properties of blended composites. The fourth section, which comes next, is about mixing natural fibers and inorganic filler with the base resin and their effect on the mechanical properties of a roto-molded product and also discusses the effect of fillers on the flow, void, and viscosity. The final section of the paper discusses several factors that can affect the properties of composites, including the particle size of natural and inorganic fillers, the heating and cooling of the mold, aging and degradation, and the rheology of the composite material. Past literature depicts that the mechanical properties of composite increase when the particle size gets smaller for both natural filler and inorganic particulate filler. This literature review has led to the following conclusion: to develop highly efficient particulate composites that can be greatly aided by careful selection of the base resin, additives, and parameter characterization. [ABSTRACT FROM AUTHOR]

Purpose of Review: Myocardial infarction with nonobstructive coronary arteries (MINOCA) is defined as acute myocardial infarction (MI) with angiographically no obstructive coronary artery disease or stenosis ≤ 50%. MINOCA is diagnostically challenging and complex, making it difficult to manage effectively. This condition accounts for 6–8% of all MI and poses an increased risk of morbidity and mortality after diagnosis. Prompt recognition and targeted management are essential to improve outcomes and our understanding of this condition, but this process is not yet standardized. This article offers a comprehensive review of MINOCA, delving deep into its unique clinical profile, invasive and noninvasive diagnostic strategies for evaluating MINOCA in light of the lack of widespread availability for comprehensive testing, and current evidence surrounding targeted therapies for patients with MINOCA. Recent Findings: MINOCA is not uncommon and requires comprehensive assessment using various imaging modalities to evaluate it further. Summary: MINOCA is a heterogenous working diagnosis that requires thoughtful approach to diagnose the underlying disease responsible for MINOCA further. [ABSTRACT FROM AUTHOR]

Purpose: Cardiac radioablation (cRA) using a stereotactic single-session radioablative approach has recently been described as a possible treatment option for patients with otherwise untreatable recurrent ventricular tachycardia (VT). There is very limited experience in cRA for patients undergoing left ventricular assist device (LVAD) therapy. We present clinical experiences of two patients treated with cRA for incessant VT under long-term LVAD therapy. Methods: Two male patients (54 and 61 years old) with terminal heart failure under LVAD therapy (both patients for 8 years) showed incessant VT despite extensive antiarrhythmic drug therapy and repeated catheter ablation. cRA with a single dose of 25 Gy was applied as a last resort strategy under compassionate use in both patients following an electroanatomical mapping procedure. Results: Both patients displayed ongoing VT during and after the cRA procedure. Repeated attempts at post-procedural rhythm conversion failed in both patients; however, one patient was hemodynamically stabilized and could be discharged home for several months before falling prey to a fatal bleeding complication. The second patient initially stabilized for a few days following cRA before renewed acceleration of running VT required bilateral ablation of the stellate ganglion; the patient died 50 days later. No immediate side effects of cRA were detected in either patient. Conclusion: cRA might serve as a last resort strategy for patients with terminal heart failure undergoing LVAD therapy and displaying incessant VT. Intermediate- and long-term outcomes of these seriously ill patients often remain poor; therefore, best supportive care strategies should also be evaluated as long as no clear beneficial effects of cRA procedures can be shown. For patients treated with cRA under running ventricular rhythm abnormality, strategies for post-procedural generation of stabilized rhythm have to be established. [ABSTRACT FROM AUTHOR]

Advances in computational algorithms and tools have made the prediction of cancer patient outcomes using computational pathology feasible. However, predicting clinical outcomes from pre-treatment histopathologic images remains a challenging task, limited by the poor understanding of tumor immune micro-environments. In this study, an automatic, accurate, comprehensive, interpretable, and reproducible whole slide image (WSI) feature extraction pipeline known as, IMage-based Pathological REgistration and Segmentation Statistics (IMPRESS), is described. We used both H&E and multiplex IHC (PD-L1, CD8+, and CD163+) images, investigated whether artificial intelligence (AI)-based algorithms using automatic feature extraction methods can predict neoadjuvant chemotherapy (NAC) outcomes in HER2-positive (HER2+) and triple-negative breast cancer (TNBC) patients. Features are derived from tumor immune micro-environment and clinical data and used to train machine learning models to accurately predict the response to NAC in breast cancer patients (HER2+ AUC = 0.8975; TNBC AUC = 0.7674). The results demonstrate that this method outperforms the results trained from features that were manually generated by pathologists. The developed image features and algorithms were further externally validated by independent cohorts, yielding encouraging results, especially for the HER2+ subtype. [ABSTRACT FROM AUTHOR]

Purpose: The recent WHO classification of breast cancer (2019) categorizes breast carcinoma with neuroendocrine (NE) differentiation into three morphologically distinct subtypes: well-differentiated neuroendocrine tumor (NET), poorly differentiated neuroendocrine carcinoma (NEC), and invasive breast carcinoma, no special type with neuroendocrine differentiation (IBC-NST-NE). Data regarding the prognostic significance of neuroendocrine differentiation are conflicting and an association, if any, between p53 mutation and neuroendocrine differentiation is largely unknown. Methods: We examined p53 expression and other clinicopathologic characteristics in three types of invasive breast carcinoma with NE differentiation in a cohort of sixty-three patients, including 45 IBC-NST with NE differentiation, 10 NETs, and 8 NECs. Results: No significant difference of clinicopathologic feature was observed between IBC-NST with NE differentiation and NET, but NECs showed significantly lower expressions of hormone receptors, more mutated p53, and higher frequency of distant metastases than IBC-NST with NE differentiation and NETs. Conclusion: NECs of the breast are genetically and clinically different from IBC-NST-NEs and NETs of the breast. [ABSTRACT FROM AUTHOR]

The significant contribution of NOx and CO2 emissions with Diesel engines and stringent European Standard norms have compelled many researchers to seek new technologies for an effective solution. Exhaust gas recirculation (EGR) can control NOx emission but at the cost of increasing CO2 emission. This trade-off is addressed in this research work where the theoretical design of a Diesel engine retrofitted with devices for simultaneous mitigation of NOx and CO2 has been presented. The simulation of the combustion process of the Diesel engine has been performed by the commercial software ANSYS which indicates 32.9%, 50.63%, and 54.43% reduction of NO2 with 10%, 20%, and 30% EGR ratio, respectively, while the corresponding increase of CO2 is 4.76%, 9.52%, and 15.28%, respectively. The mitigation of this increased amount of CO2 has been demonstrated by carrying out experimental investigations on Diesel engine exhaust with carbon capture unit using two standalone absorbents, viz. aqueous ammonia (AQ_NH3) and mono-ethanol-amine (MEA) at five different brake power values. Average carbon capture efficiency is found to be 91% and 94% with AQ_NH3 and MEA, respectively. Further, the blend consisting of 67% of AQ_NH3 and 33% of MEA has also been investigated which shows 95% carbon capture efficiency. This work revealed that the EGR and carbon capture unit in the Diesel engine will be an effective solution to control NOx and CO2 emissions simultaneously and provide the basis for future research on the execution of stringent European Standard norms. [ABSTRACT FROM AUTHOR]

Despite technological advances in the analysis of digital images for medical consultations, many health information systems lack the ability to correlate textual descriptions of image findings linked to the actual images. Images and reports often reside in separate silos in the medical record throughout the process of image viewing, report authoring, and report consumption. Forward-thinking centers and early adopters have created interactive reports with multimedia elements and embedded hyperlinks in reports that connect the narrative text with the related source images and measurements. Most of these solutions rely on proprietary single-vendor systems for viewing and reporting in the absence of any encompassing industry standards to facilitate interoperability with the electronic health record (EHR) and other systems. International standards have enabled the digitization of image acquisition, storage, viewing, and structured reporting. These provide the foundation to discuss enhanced reporting. Lessons learned in the digital transformation of radiology and pathology can serve as a basis for interactive multimedia reporting (IMR) across image-centric medical specialties. This paper describes the standard-based infrastructure and communications to fulfill recently defined clinical requirements through a consensus from an international workgroup of multidisciplinary medical specialists, informaticists, and industry participants. These efforts have led toward the development of an Integrating the Healthcare Enterprise (IHE) profile that will serve as a foundation for interoperable interactive multimedia reporting. [ABSTRACT FROM AUTHOR]

The biomaterial with the highest known tensile strength is a unique composite of chitin and goethite (α-FeO(OH)) present in teeth from the Common Limpet (Patella vulgata). A biomimetic based on limpet tooth, with corresponding high-performance mechanical properties is highly desirable. Here we report on the replication of limpet tooth developmental processes ex vivo, where isolated limpet tissue and cells in culture generate new biomimetic structures. Transcriptomic analysis of each developmental stage of the radula, the organ from which limpet teeth originate, identifies sequential changes in expression of genes related to chitin and iron processing. We quantify iron and chitin metabolic processes in the radula and grow isolated radula cells in vitro. Bioinspired material can be developed with electrospun chitin mineralised by conditioned media from cultured radula cells. Our results inform molecular processes behind the generation of limpet tooth and establish a platform for development of a novel biomimetic with comparable properties. The highest tensile strength biomaterial known exists in limpet teeth and replicating this material is of interest. Here, the authors report on the ex vivo growth of teeth and use of isolated limpet tissue and cells providing foundations for the development of this high-tensile biomaterial. [ABSTRACT FROM AUTHOR]

The heat transfer analysis in a helical coil tube heat exchanger is challenging due to the complex flow field developed by the tube curvature. In this paper, estimation of uneven local heat flux is carried out at the fluid–solid interface in a helical coil tube heat exchanger for laminar and turbulent flow in two different ways. First, the governing continuity, momentum, and energy equations of working fluid for laminar and turbulent flow are solved to determine the heat flux at the fluid–solid interface with commercial CFD software Ansys Fluent. This heat flux is then used as a boundary condition to solve the governing equation of heat conduction in tube thickness by finite volume discretization method to obtain temperature field at the outer tube surface. The heat flux is now considered unknown and estimated with the newly developed enhanced conjugate gradient method (ECGM). ECGM has been designed to enhance the performance of traditional CGM by coupling with the stochastic Jaya algorithm. Ethylene glycol and water has been selected as a working fluid for laminar and turbulent flow, respectively. The average percentage error with ECGM in the estimation of heat flux profile obtained by CFD software in laminar flow and turbulent flow is 0.32 and 0.18 respectively. Even after adding random errors in the simulated temperature field, the ECGM algorithm produces a reasonable and stable solution. [ABSTRACT FROM AUTHOR]

Climate change and global warming are the visible consequences of the increased amount of carbon dioxide (CO2) in the atmosphere. Among the various sources of anthropogenic CO2 emission, the diesel engine has a significant contribution. The development of a reliable system to efficiently minimize CO2 emissions from diesel engines to the safest level is lacking in the open literature. Therefore, a comprehensive multidisciplinary approach has been applied in this paper to investigate the efficacy of the post-combustion carbon capture (PCC) process for the diesel engine. The experiments have been performed on the exhaust of a direct injection diesel engine at five different brake powers with blends of aqueous ammonia (AQ_NH3), monoethanolamine (MEA), N,N-dimethylethanolamine (DMEA), and 1-ethyl-3-methylimidazolium tetrafluoroborate (C2mim BF4) ionic liquid (IL) as an absorbent for CO2 capture. The reaction mechanism of these absorbent with CO2 are also studied by the geometrical, energetical, MESP, frontier molecular orbitals, and NBO analysis using the first-principles density functional theory (DFT) calculations. The maximum CO2 absorption efficiency of almost 97% was achieved for the blend consisting of 67% of AQ_NH3 and 33% of MEA. Moreover, AQ_MEA and blend of AQ_NH3, DMEA, and C2mim BF4 ionic liquid showed 96% and 94% CO2 absorption efficiency, respectively. [ABSTRACT FROM AUTHOR]

Purpose: Patients with systemic sclerosis (SSc) often suffer from premature tooth loss. This is a retrospective case series of patients with systemic sclerosis who were treated with dental implants. Methods: SSc patients treated with at least one dental implant between 5 August 1998 and 31 December 2018 were included in this long-term retrospective study. The primary study variables were the plaque index (PLI), sulcus bleeding index (SBI), peri-implant pocket depth (PPD) and interincisal distance (ID). The test for marginal homogeneity analysed whether the SBI and PLI values changed between examination and follow-up. A linear regression was performed for the PPD measurement. The rank correlation coefficient compared the SBI with the PLI and the PPD with the PLI. The survival rate data for the implants were analysed by the Kaplan–Meier procedure. P <.05 was considered significant. Results: Twenty-four patients [(age: mean 59.6 years (SD ± 13.08)] received a total of 72 implants. ID resulted in a mean value of 29.54 mm (SD ± 6.4 mm). The mean value of the PPD was between 2.4 mm and 2.8 mm. A comparison of the SBI with the PLI and the PPD with the PLI showed a significantly positive correlation between the SBI and the PLI and between the PPD and the PLI. The correlation between the PPD and the PLI (Spearman rho: 0.36, p < 0.001) was less pronounced than that between the SBI and the PLI (Spearman rho: 0.61, p < 0.001). Kaplan–Meier analysis showed a post-10-year implant survival rate of 87.6% (95%-KI: 75.5–94.0). Conclusion: Implant-supported oral rehabilitation can be carried out and maintained successfully in SSc patients. [ABSTRACT FROM AUTHOR]

Purpose of Review: To give an overview of the role of social media (SoMe) in cardio-oncology during the COVID-19 pandemic. Recent Findings: SoMe has been critical in fostering education, outreach, awareness, collaboration, dissemination of information, and advocacy in cardio-oncology. This has become increasingly evident during the COVID-19 pandemic, during which SoMe has helped share best practices, community, and research focused on the impact of COVID-19 in cardiology and hematology/oncology, with cardio-oncology at the interface of these two subspecialty fields. Summary: A strength of SoMe is the ability to amplify a message in real-time, globally, with minimal investment of resources. This has been particularly beneficial for the emerging field of cardio-hematology/cardio-oncology, a field focused on the interplay of cancer and cardiovascular disease. SoMe field especially during the COVID-19 pandemic. We illustrate how social media has supported innovation (including telemedicine), amplification of healthcare workers' voice, and illumination of pre-existing and continued health disparities within the field of cardio-oncology during the pandemic. [ABSTRACT FROM AUTHOR]

Background/objective: Inter-hospital patient transfers for neurocritical care are increasingly common due to increased regionalization for acute care, including stroke and intracerebral hemorrhage. This process of transfer is uniquely vulnerable to errors and risk given numerous handoffs involving multiple providers, from several disciplines, located at different institutions. We present failure mode and effect analysis (FMEA) as a systems engineering methodology that can be applied to neurocritical care transitions to reduce failures in communication and improve patient safety. Specifically, we describe our local implementation of FMEA to improve the safety of inter-hospital transfer for patients with intracerebral and subarachnoid hemorrhage as evidence of success. Methods: We describe the conceptual basis for and specific use-case example for each formal step of the FMEA process. We assembled a multi-disciplinary team, developed a process map of all components required for successful transfer, and identified "failure modes" or errors that hinder completion of each subprocess. A risk or hazard analysis was conducted for each failure mode, and ones of highest impact on patient safety and outcomes were identified and prioritized for implementation. Interventions were then developed and implemented into an action plan to redesign the process. Importantly, a comprehensive evaluation method was established to monitor outcomes and reimplement interventions to provide for continual improvement. Results: This intervention was associated with significant reductions in emergency department (ED) throughput (ED length of stay from 300 to 149 min, (p <.01), and improvements in inter-disciplinary communication (increase from pre-intervention (10%) to post- (64%) of inter-hospital transfers where the neurological intensive care unit and ED attendings discussed care for the patient prior to their arrival). Conclusions: Application of the FMEA approach yielded meaningful and sustained process change for patients with neurocritical care needs. Utilization of FMEA as a change instrument for quality improvement is a powerful tool for programs looking to improve timely communication, resource utilization, and ultimately patient safety. [ABSTRACT FROM AUTHOR]

Purpose: Two types of macrophages are present in tumor microenvironment. M1 macrophages exhibit potent anti-tumor properties, while M2 macrophages play the pro-tumoral roles. The presence of M2 macrophages is associated with worsened overall survival in triple-negative breast carcinoma (TNBC) patients. However, the relationship between M2 macrophages and response to neoadjuvant chemotherapy (NAC) is unknown. Methods: M2 macrophages were investigated on biopsy whole sections from 66 TNBCs treated with NAC by CD163 together with other immune checkpoint markers (PD1, PD-L1 and CD8) using a multi-color immunohistochemical multiplex assay. Results: Incomplete response was significantly associated with older age, lower PD-L1 expression (tumor and stroma), lower levels of CD8-positive TILs in stroma, but higher level of CD163-positive macrophages, with the level of CD163-positive M2 macrophages in peritumoral area as the strongest factor. Conclusions: Our data have demonstrated that the level of CD163-positive M2 macrophages was significantly higher in TNBC patients with incomplete response than patients with complete response, suggesting M2 macrophages' important role in predicting TNBC patients' response to NAC. [ABSTRACT FROM AUTHOR]

Diagnostic and evidential static image, video clip, and sound multimedia are captured during routine clinical care in cardiology, dermatology, ophthalmology, pathology, physiatry, radiation oncology, radiology, endoscopic procedural specialties, and other medical disciplines. Providers typically describe the multimedia findings in contemporaneous electronic health record clinical notes or associate a textual interpretative report. Visual communication aids commonly used to connect, synthesize, and supplement multimedia and descriptive text outside medicine remain technically challenging to integrate into patient care. Such beneficial interactive elements may include hyperlinks between text, multimedia elements, alphanumeric and geometric annotations, tables, graphs, timelines, diagrams, anatomic maps, and hyperlinks to external educational references that patients or provider consumers may find valuable. This HIMSS-SIIM Enterprise Imaging Community workgroup white paper outlines the current and desired clinical future state of interactive multimedia reporting (IMR). The workgroup adopted a consensus definition of IMR as "interactive medical documentation that combines clinical images, videos, sound, imaging metadata, and/or image annotations with text, typographic emphases, tables, graphs, event timelines, anatomic maps, hyperlinks, and/or educational resources to optimize communication between medical professionals, and between medical professionals and their patients." This white paper also serves as a precursor for future efforts toward solving technical issues impeding routine interactive multimedia report creation and ingestion into electronic health records. [ABSTRACT FROM AUTHOR]

Limited studies on whole slide imaging (WSI) in surgical neuropathology reported a perceived limitation in the recognition of mitoses. This study analyzed and compared the inter- and intra-observer concordance for atypical meningioma, using glass slides and WSI. Two neuropathologists and two residents assessed the histopathological features of 35 meningiomas—originally diagnosed as atypical—in a representative glass slide and corresponding WSI. For each histological parameter and final diagnosis, we calculated the inter- and intra-observer concordance in the two viewing modes and the predictive accuracy on recurrence. The concordance rates for atypical meningioma on glass slides and on WSI were 54% and 60% among four observers and 63% and 74% between two neuropathologists. The inter-observer agreement was higher using WSI than with glass slides for all parameters, with the exception of high mitotic index. For all histological features, we found median intra-observer concordance of ≥ 79% and similar predictive accuracy for recurrence between the two viewing modes. The higher concordance for atypical meningioma using WSI than with glass slides and the similar predictive accuracy for recurrence in the two modalities suggest that atypical meningioma may be safely diagnosed using WSI. [ABSTRACT FROM AUTHOR]

The task of pedestrian detection in video surveillance applications will face challenges like dynamic background changes, false human detection (shadow), and illumination variations. In literature, many approaches have been proposed to resolve these challenges. But their performance is not up to the mark. Thus this paper proposes efficient pedestrian detection including shadow removal and automatic dynamic background update. For this firstly, a background frame is initialized where no moving object is present. Then a background subtraction algorithm is applied to each of the key frames from the live video to detect the foreground objects (using fuzzy C means clustering followed by mean absolute difference). Later on this segmented foreground a contour is estimated and passed through the HOG classifier for pedestrian detection. The performance of the proposed approach has been compared using various datasets & state-of-the-art approaches and found to the best with an average precision of 98 %, unlike the others. [ABSTRACT FROM AUTHOR]

Purpose: Human epidermal growth factor receptor 2 (HER2) intratumoral heterogeneity (ITH) occurs in a subset of breast cancers. Our recent study revealed it as an independent predictive factor for the response to anti-HER2 neoadjuvant therapy. In this study, we aimed to investigate its association with distal metastasis. Methods: HER2 ITH was assessed using HER2 gene protein assay (GPA) on whole tissue sections of pretreatment biopsies from a cohort of 158 HER2-positive invasive breast carcinomas and correlated with patients' clinical follow-up outcomes along with other clinicopathologic characteristics. Results: Fifty-seven cases (36%) showed HER2 ITH including 19 with genetic, 8 with both genetic and non-genetic, and 30 with non-genetic ITH. Multivariate analysis demonstrated larger tumor size, positive resected lymph node(s), negative PR, and the presence of HER2 ITH were independently associated with distal metastasis. Additionally, multivariate analysis demonstrated larger tumor size and the presence of HER2 ITH were the only independent factors associated with decreased overall survival (death). Conclusion: The presence of HER2 ITH is an independent factor associated with poor overall survival and increased distal metastasis in HER2-positive breast cancer patients. [ABSTRACT FROM AUTHOR]

Copyright of Herz is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: Patients with HER2-positive breast cancer commonly receive anti-HER2 neoadjuvant chemotherapy and pathologic complete response (pCR) can be achieved in up to half of the patients. HER2 protein expression detected by immunohistochemistry (IHC) can be quantified using digital imaging analysis (DIA) as a value of membranous connectivity. We aimed to investigate the association HER2 IHC DIA quantitative results with response to anti-HER2 neoadjuvant chemotherapy. Methods: Digitized HER2 IHC whole slide images were analyzed using Visiopharm HER2-CONNECT to obtain quantitative HER2 membranous connectivity from a cohort of 153 HER2+ invasive breast carcinoma cases treated with anti-HER2 neoadjuvant chemotherapy (NAC). HER2 connectivity and other factors including age, histologic grade, ER, PR, and HER2 fluorescence in situ hybridization (FISH) were analyzed for association with the response to anti-HER2 NAC. Results: Eighty-three cases (54.2%) had pCR, while 70 (45.8%) showed residual tumor. Younger age, negative ER/PR, higher HER2 DIA connectivity, higher HER2 FISH ratio and copy number were significantly associated with pCR in univariate analysis. Multivariate analysis demonstrated only age, HER2 DIA connectivity, PR negativity, and HER2 copy number was significantly associated with pCR, whereas HER2 DIA connectivity had the strongest association. Conclusions: HER2 IHC DIA connectivity is the most important factor predicting pCR to anti-HER2 neoadjuvant chemotherapy in patients with HER2-positive breast cancer. [ABSTRACT FROM AUTHOR]

Purpose of the Review: The purpose of this study is to review the utility of cardiac magnetic resonance (CMR) imaging in diagnosing and differentiating among different cardiac masses. Recent Findings: Recent advances in tissue characterization have made CMR the noninvasive modality of choice in differentiating cardiac masses. Greater spatial resolution, sophisticated tissue characterization, and multiple imaging planes to assess intra-cavitary masses enable CMR to perform a "virtual biopsy" of the mass. Summary: Cardiac tumors are rare but reporting of cardiac masses on noninvasive testing as computed tomography (CT) or echocardiogram is common. Cardiac masses can widely range from a normal structure of the heart, also known as "pseudo-mass," to cardiac thrombus, to the benign and malignant primary and secondary tumors of the heart. CMR represents an advanced noninvasive method to differentiate between cardiac masses given its spatial and tissue characterization ability. It has become a key testing tool in the diagnostic algorithm of evaluating cardiac masses. [ABSTRACT FROM AUTHOR]

Silica aerogels are prepared by drying wet-gels under conditions that eliminate surface tension forces, typically by exchanging the pore-filling solvent with liquid or supercritical fluid (SCF) CO2 that is vented off like a gas. Thereby, silica wet-gels should not shrink during drying, but they do. According to the literature, most shrinkage (~71%) happens during depressurization of the autoclave. Here, based on prior literature, and working with wet-gels obtained via base-catalyzed gelation of tetramethylorthosilicate (TMOS), the basic hypothesis was that depressurization shrinkage takes place at the primary/secondary particle level. For this to happen there has to be available space to accommodate merging secondary particles, and a driving force. Secondary particles are mass fractals (by SAXS) and their empty space can accommodate primary particles from neighboring assemblies. The driving force was assumed to be H-bonding developing between surface silanols as soon as all fluids are removed from the pores. That hypothesis was put to test by replacing gelation solvents with nonhydrogen bonding toluene or xylene. Indeed, while the total drying shrinkage of toluene- or xylene-filled wet-gels was equal to that observed with aerogels obtained from acetone-filled wet-gels (~8–9%), the major part of that shrinkage (~74%) was transferred to the wet-gel stage. The remaining shrinkage (~26%) was assigned to interfacial tension forces between the pore-filling solvent and liquid or SCF CO2. Having transferred the major part of drying shrinkage to the wet-gel stage has technological implications, because it is easier to manipulate gels at that stage. Furthermore, our results underline that optimization of the drying process should take into account the fact that drying of silica wet-gels into aerogels is a two-stage moving boundary problem. Highlights: The major part of the shrinkage during drying silica wet-gels to aerogels with SCF CO2 is associated with the depressurization phase of the drying process. A part of the shrinkage equal to that reported as depressurization shrinkage (70–75%) has been transferred to the wet-gel phase of processing. The remaining part of the drying shrinkage has been assigned to interfacial tension. The practical significance of those findings is related to the fact that it is easier to control shrinkage at the wet-gel phase of processing. From a theoretical perspective, drying with SCF CO2 is a two-stage moving boundary problem. [ABSTRACT FROM AUTHOR]

Copyright of Herzschrittmachertherapie und Elektrophysiologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Salivary duct carcinomas (SDC) and Her2/Neu3-overexpressing invasive breast carcinomas (HNPIBC/IBC) are histologically indistinguishable. We investigated whether common histopathologic and immunophenotypic features of SDC and IBC are mirrored by a similar microRNA (miRNA) profile. MiRNA profiling of 5 SDCs, 6 IBCs Her2/Neu3+, and 5 high-grade ductal breast carcinoma in situ (DCIS) was performed by NanoString platform. Selected miRNAs and HOXA1 gene were validated by RT-PCR. We observed similar miRNA expression profiles between IBC and SDC with the exception of 2 miRNAs, miR-10a and miR-142-3p, which were higher in IBC tumors. DCIS tumors displayed increased expression of miR-10a, miR-99a, miR-331-3p and miR-335, and decreased expression of miR-15a, miR-16 and miR-19b compared to SDC. The normal salivary gland and breast tissues also showed similar expression profiles. Interestingly, miR-10a was selectively increased in both IBC and normal breast tissue compared to SDC and normal salivary gland tissue. Moreover, our NanoString and RT-PCR data confirmed that miR-10a was upregulated in IBC and DCIS compared to SDC. Finally, we show downregulation of HOXA1, a miR-10 target, in IBC tumors compared to normal breast tissue. Taken together, our data demonstrates that, based on miRNA profiling, SDC is closely related to HNPIBC. Our results also suggest that miR-10a is differentially expressed in IBC compared to SDC and may have potential utility as a diagnostic biomarker in synchronous or metachronous malignant epithelial malignancies involving both organs. In addition, miR-10a could be playing an important role as a mammary-specific oncogene, involved in breast cancer initiation (DCIS) and progression (IBC), through mechanisms that include modulation of HOXA1 gene expression. [ABSTRACT FROM AUTHOR]

Heart failure and atrial fibrillation are common and responsible for significant mortality of patients. Both share the same risk factors like hypertension, ischemic heart disease, diabetes, obesity, arteriosclerosis, and age. A variety of microscopic and macroscopic changes favor the genesis of atrial fibrillation in patients with preexisting heart failure, altered subcellular Ca2+ homeostasis leading to increased cellular automaticity as well as concomitant fibrosis that are induced by pressure/volume overload and altered neurohumoral states. Atrial fibrillation itself promotes clinical deterioration of patients with preexisting heart failure as atrial contraction significantly contributes to ventricular filling. In addition, atrial fibrillation induced tachycardia can even further compromise ventricular function by inducing tachycardiomyopathy. Even though evidence has been provided that atrial functions significantly and independently of confounding ventricular pathologies, correlate with mortality of heart failure patients, rate and rhythm controls have been shown to be of equal effectiveness in improving mortality. Yet, it also has been shown that cohorts of patients with heart failure benefit from a rhythm control concept regarding symptom control and hospitalization. To date, amiodarone is the most feasible approach to restore sinus rhythm, yet its use is limited by its extensive side-effect profile. In addition, other therapies like catheter-based pulmonary vein isolation are of increasing importance. A wide range of heart failure-specific therapies are available with mixed impact on new onset or perpetuation of atrial fibrillation. This review highlights pathophysiological concepts and possible therapeutic approaches to treat patients with heart failure at risk for or with atrial fibrillation. [ABSTRACT FROM AUTHOR]

Background: Catheter ablation of left atrial linear lesions is an effective treatment option for perimitral flutter and is often used as a substrate modification approach for persistent atrial fibrillation. The two most popular mitral isthmus lines are those of the anterior or the posterior mitral isthmus. A comparison of these two mitral isthmus ablation approaches is still pending.Methods: Patients undergoing catheter ablation either at the anterior or the posterior mitral isthmus were included. Procedural success, conduction block, procedure durations, complications, and the necessity of a coronary sinus ablation were analyzed.Results: We investigated 80 consecutive patients, 40 (50%) with an anterior and 40 (50%) with a posterior mitral isthmus line. Twenty (25.0%) patients had perimitral annulus flutter; the remainder of the patients had persistent atrial fibrillation. Bidirectional conduction block was achieved in the same proportion in the anterior group (36; 90.0%) as it was in the posterior group (30; 75.0%) (statistically insignificant). Duration of procedure (18 ± 12 vs. 34 ± 24 min, p = 0.001), radiofrequency application (11 ± 7 vs. 18 ± 11 min, p = 0.004), and fluoroscopy (2 ± 2 vs. 8 ± 8 min, p < 0.001) values were all significantly lower in the anterior group. Only patients in the posterior line group had to be ablated via the coronary sinus 24 (60.0 %).Conclusions: Ablation at the anterior mitral isthmus shows the same success rate as the posterior mitral isthmus does. Catheter ablation at the anterior mitral isthmus is associated with significantly shorter procedure durations without the need of a coronary sinus ablation. [ABSTRACT FROM AUTHOR]

Purpose: Anti-HER2 neoadjuvant chemotherapy has been widely used in HER2-positive breast cancer patients; however, pathologic complete response (pCR) is achieved in only 40-50% of patients. The aim of this study was to investigate the association of HER2 intratumoral heterogeneity (ITH) with response to anti-HER2 neoadjuvant chemotherapy. Methods: Assessment of HER2 ITH was performed on whole tissue sections of pre-treatment samples from a cohort of 64 invasive breast carcinoma cases originally considered positive for HER2 and treated with anti-HER2 neoadjuvant chemotherapy. Both HER2 gene signal and protein expression were simultaneously evaluated by means of a single-slide dual assay, designated as a HER2 gene-protein assay (GPA). HER2 GPA was carried out as well on surgical resection tissues from 25 cases with incomplete therapeutic response. Results: Nineteen of 64 cases (30%) showed HER2 ITH. Significantly more cases with HER2 ITH were found in the incomplete response group (56%, 14/25) than in the pCR group (13%, 5/39). Patients without ITH detectable by GPA had a 76% pCR outcome (34/45), as compared to 26% (5/19) for those with detectable ITH. Multivariate analysis demonstrated HER2 ITH, progesterone receptor positivity, and relatively low HER2/chromosome 17 centromere ratio to be significantly associated with incomplete response. Conclusions: HER2 ITH analyses conducted with GPA method revealed that HER2 ITH is an independent factor predicting incomplete response to anti-HER2 neoadjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

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Given a group action on a surface with a finite invariant set we investigate how the algebraic properties of the induced group of permutations of that set affects the dynamical properties of the group. Our main result shows that in many circumstances if the induced permutation group is not solvable then among the homeomorphisms in the group there must be one with a pseudo-Anosov component. We formulate this in terms of the mapping class group relative to the finite set and show the stronger result that in many circumstances (e.g. if the surface has boundary) if this mapping class group has no elements with pseudo-Anosov components then it is itself solvable. [ABSTRACT FROM AUTHOR]

Catheter tissue contact force (CF) is an important factor for durable lesion formation during radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF). Since CF varies in the beating heart, atrial rhythm during RFCA may influence CF. A high-density map and RFCA points were obtained in 25 patients undergoing RFCA of AF using a CF-sensing catheter (Tacticath, St. Jude Medical). The operators were blinded to the CF information. Contact type was classified into three categories: constant, variable, and intermittent contact. Average CF and contact type were analyzed according to atrial rhythm (SR vs. AF) and anatomical location. A total of 1364 points (891 points during SR and 473 points during AF) were analyzed. Average CFs showed no significant difference between SR (17.2 ± 11.3 g) and AF (17.2 ± 13.3 g; p = 0.99). The distribution of points with an average CF of ≥20 and <10 g also showed no significant difference. However, the distribution of excessive CF (CF ≥40 g) was significantly higher during AF (7.4 %) in comparison with SR (4.2 %; p < 0.05). At the anterior area of the right inferior pulmonary vein (RIPV), the average CF during AF was significantly higher than during SR ( p < 0.05). Constant contact was significantly higher during AF (32.2 %) when compared to SR (9.9 %; p < 0.01). Although the average CF was not different between atrial rhythms, constant contact was more often achievable during AF than it was during SR. However, excessive CF also seems to occur more frequently during AF especially at the anterior part of RIPV. [ABSTRACT FROM AUTHOR]

Background: Catheter ablation has become a standard curative treatment for symptomatic, drug refractory premature ventricular contractions (PVC). The aim of this study was to investigate the efficacy and safety of this procedure in elderly patients. Methods and results: A total of 101 consecutive patients (mean age 50.7 ± 16.9, 53 % women) presenting to our center for ablation of PVC were included and assigned to two age groups (<65 and ≥65 years). Clinical characteristics, procedural parameters, complications and success after 6-month follow up were compared between the two groups. Patients ≥65 years ( n = 27) showed a higher rate of hypertension (78 vs. 27 %, p < 0.001), coronary artery disease (19 vs. 12 %, p = 0.01), renal insufficiency (22 vs. 1 %, p < 0.001) and diabetes (22 vs. 3 %, p = 0.001). Left ventricular ejection fraction did not differ between the two groups (56.6 vs. 57.4 %, p = 0.497). In patients <65 years the origin of the PVC was significantly more often in RVOT or LVOT (95 vs. 70 %, p = 0.001). Acute success rates (67 vs. 73 %, p = 0.545) and success rates after 6 months (81 vs. 86 %, p = 0.795) were not different between the two groups. Two complications were observed, both occurred in the <65 years group (1 pericardial effusion and 1 large groin hematoma). Conclusion: Catheter ablation of PVC is feasible in elderly patients without overt heart disease. Success rates are not significantly different compared to patients <65 years. Procedural complications are rare in both the groups. Ablation of this arrhythmia can therefore be regarded as a promising curative treatment in advanced age. [ABSTRACT FROM AUTHOR]